Affected male patients present moderate to severe intellectual disability, hypotonia, severe developmental delay, early-onset complex partial or tonic-clonic seizures, strabismus, dysmetria and occasionally ataxia. [bioportal.bioontology.org]

Our proband presented an occipital arachnoid cyst without any other modifications. [journals.lww.com]

III.2 presents both atonic and tonic-clonic seizures, whereas III.4 presents atonic seizures. Their mother (II.2) has also documented epilepsy (not infantile), presented as generalized tonic-clonic seizures. [nature.com]

Although it is present in approximately 0.15-0.3% of males, most of the genetic defects associated with MRX, which may involve more than ten different genes, remain unknown. Here we report ... [more] [thebiogrid.org]

The presentation and severity can vary from individual to individual. Affected females demonstrate a milder form of the disorder. [ophn1.org]

• Disability

  Affected male patients present moderate to severe intellectual disability, hypotonia, severe developmental delay, early-onset complex partial or tonic-clonic seizures, strabismus, dysmetria and occasionally ataxia. [bioportal.bioontology.org]

  XLMR, X-linked intellectual disability; OPHN1- related XLID; Oligophrenin-1 syndrome; X-linked Intellectual Deficit with Cerebellar Hypoplasia; X-linked intellectual disability-cerebellar hypoplasia syndromeIntellectual disability, X-linked, with cerebellar [rarediseases.info.nih.gov]

  Overview OPHN1 syndrome is a rare disorder characterized by intellectual disability and changes in the part of the brain which controls movement and balance (cerebellum). The syndrome mainly affects males. [rarediseases.org]

  Oligophrenin-1 (OPHN1) encodes a Rho GTPase-activating protein (RhoGAP) whose loss of function is associated with a rare X-linked intellectual disability (X-LID), with specific features and cerebellar hypoplasia involving the vermis. [ejpn-journal.com]

  […] with X-linked intellectual disability (XLID) associated with cerebellar hypoplasia and ventriculomegaly, suggesting it could be a recognizable syndromic intellectual disability (ID). [okina.univ-angers.fr]

• Asymptomatic

  […] the distinctive feature that the phenotype is expressed largely in females with mutations and not males.13 As would be expected in an X-linked condition, there is wide variability in the phenotype of female carriers of OPHN1 mutations, ranging from asymptomatic [dovepress.com]

  Because of the phenotypic variability of the XLID, carries are frequently reported as asymptomatic with a non-specific and mild phenotype (strabismus and learning difficulties). [journals.lww.com]

• Long Arm

  The array-CGH analysis by using CytoSure needle ISCA V2.0 8X60K OGT (Oxford Gene Technology, United Kingdom) identified a microdeletion of the long arm of the Xq12 region extended about 16 Kb, of maternal origin with the array-CGH formula according to [journals.lww.com]

  […] and the distal portion of the long arm (data not shown). [jmg.bmj.com]

• Strabismus

  Affected male patients present moderate to severe intellectual disability, hypotonia, severe developmental delay, early-onset complex partial or tonic-clonic seizures, strabismus, dysmetria and occasionally ataxia. [bioportal.bioontology.org]

  Inheritance is X-linked.[12078] Some females who carry a mutation in the OPHN1 gene may have mild learning disabilities, mild cognitive impairment, strabismus, and subtle facial changes.[12078][12080][12082] For more information, visit GARD. [rarediseases.org]

  Some females who carry a genetic change in the OPHN1 gene may have mild learning disabilities, mild cognitive impairment, strabismus, and subtle facial changes. Estimated Number of People with this Disease This section is currently in development. [rarediseases.info.nih.gov]

  The cerebellum is involved in oculomotor coordination, which may contribute to nystagmus and strabismus. [journals.lww.com]

  The mutation is associated with intellectual disability, epilepsy, developmental delay, strabismus, a hypoplastic cerebellum and autistic features. The presentation and severity can vary from individual to individual. [ophn1.org]

• Abnormal Behavior

  Signs and symptoms may include intellectual disability, low muscle tone (hypotonia), developmental and cognitive delay, early-onset seizures, abnormal behavior, small or underdeveloped genitals, characteristic facial features (long face, bulging forehead [rarediseases.org]

  ORPHA:96121 Mend Syndrome Hydrocephalus, Hyperactivity, Abnormal social behavior, Aggressive behavior, Dandy-Walker malform... [mousephenotype.org]

• Cryptorchidism

  Cryptorchidism and genital hypoplasia have been reported. Various mutations including deletions and splice site mutations in the OPHN1 gene (Xq12) have been reported in patients with this syndrome. [bioportal.bioontology.org]

  Several authors reported cases with cryptorchidism, micropenis, hypoplastic scrotum connected with the OPHN1 gene,[3,22,24] but in our study, none of our subjects presents abnormal external genitalia. [journals.lww.com]

• Seizure

  Affected male patients present moderate to severe intellectual disability, hypotonia, severe developmental delay, early-onset complex partial or tonic-clonic seizures, strabismus, dysmetria and occasionally ataxia. [bioportal.bioontology.org]

  Signs and symptoms may include intellectual disability, low muscle tone (hypotonia), developmental and cognitive delay, early-onset seizures, abnormal behavior, small or underdeveloped genitals, characteristic facial features (long face, bulging forehead [rarediseases.org]

  Both the proband (III.2) and his affected brother (III.4) experienced early onset seizures. III.2 presents both atonic and tonic-clonic seizures, whereas III.4 presents atonic seizures. [nature.com]

  […] severe phenotypes Guo H, et al. (2018) Yes - 15 Support Characterization of intellectual disability and autism comorbidity through gene panel sequencing Aspromonte MC, et al. (2019) Yes - 16 Support - Pode-Shakked B et al. (2021) No Epilepsy/seizures [gene.sfari.org]

• Mild Cognitive Impairment

  Inheritance is X-linked.[12078] Some females who carry a mutation in the OPHN1 gene may have mild learning disabilities, mild cognitive impairment, strabismus, and subtle facial changes.[12078][12080][12082] For more information, visit GARD. [rarediseases.org]

  Some females who carry a genetic change in the OPHN1 gene may have mild learning disabilities, mild cognitive impairment, strabismus, and subtle facial changes. Estimated Number of People with this Disease This section is currently in development. [rarediseases.info.nih.gov]

• Mental Deterioration

  ORPHA:250989 Craniofacial Dyssynostosis With Short Stature Hydrocephalus, Agenesis of corpus callosum, Ventriculomegaly OMIM:218350 Infantile Neuroaxonal Dystrophy Hyperactivity, Impulsivity, Mental deterioration, Psychomotor deterioration, Emotional [mousephenotype.org]

• Dysmetria

  Affected male patients present moderate to severe intellectual disability, hypotonia, severe developmental delay, early-onset complex partial or tonic-clonic seizures, strabismus, dysmetria and occasionally ataxia. [bioportal.bioontology.org]

• Convulsions

  OMIM:611102 Acrokeratoderma, Hereditary Papulotranslucent Fine hair OMIM:101840 Loose Anagen Hair Syndrome Loose anagen hair, Fair hair, Sparse hair OMIM:600628 Alopecia-Mental Retardation Syndrome With Convulsions And Hypergonadotropic Hypogonadism Hypergonadotropic [mousephenotype.org]

[…] bulging forehead, under eye creases, deep set eyes, and large ears), crossed eyes (strabismus) and inability to coordinate movements.[12078][12079] A small cerebellum and large brain ventricles can be seen on brain imaging (MRI).[12078][12080][12082] Treatment [rarediseases.org]

XLMR; OPHN1 XLMR, X-linked intellectual disability; OPHN1- related XLID; Oligophrenin-1 syndrome; X-linked Intellectual Deficit with Cerebellar Hypoplasia; X-linked intellectual disability-cerebellar hypoplasia syndrome About the Disease Diagnosis & Treatment [rarediseases.info.nih.gov]

One of the reasons we are creating this site is because we believe there is power in numbers - to fuel medical research, clinical trials for possible treatments, and advocacy. [ophn1.org]

The deletion was determined to be a de novo variant and his family was counseled about their low recurrence risk and the patient’s prognosis. Alternative therapies for autism (vitamin supplements) were stopped by the family at that time. [dovepress.com]

[…] the skills learned and accomplished by people daily characterize adaptive behavior.[1] ID represents a reduction in cognitive abilities that appear before the age of 18 years and influences approximately 1% to 3% of the general population.[4,5] The etiology [journals.lww.com]

Although the majority of children with epilepsy or autism remain without genetic diagnoses, those who are diagnosed may derive significant benefit from determination of the genetic etiology of their symptoms.1 CMA is considered a first-line diagnostic [dovepress.com]

[…] model.28 An in vitro model using interfering ribonucleic acid knockdown in rat hippocampal neurons showed that excitatory glutamatergic synapses could be neither formed nor maintained normally in the absence of Ophn-1 expression.29 Ophn-1 knockdown also prevents [dovepress.com]

Destruction of meningeal cells over the newborn hamster cerebellum with 6-hydroxydopamine prevents foliation and lamination in the rostral cerebellum. [jmg.bmj.com]